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Central adiposity is a leading risk factor for cardiovascular disease, and genetic factors contribute both to fat distribution, measured as waist-to-hip ratio adjusted for BMI (WHRa), and to differences in central adiposity prevalence. To date, 49 loci have been associated with WHRa, based on studies of common [minor allele frequency (MAF) ≥5%] single nucleotide variants (SNVs), primarily in European descent populations. Our aim was to identify low frequency (LFV: MAF RAPGEF3 [MAF=0.01, β (SE) = -0.09 (0.012), P=1.28E-13]. In addition, one novel RV reached CWS in men for UGGT2 [MAFACVR1C [MAFRAPGEF3 (P=1.18E-11) as significantly associated with WHRa in the all ancestry sex combined analyses after correction for multiple tests (PRAPGEF3 also shows a significant association (p=4.68E-12) in all ancestry, sex combined gene-based analysis of BMI. RAPGEF3 is expressed in subcutaneous and visceral adipose tissue, and has been implicated in insulin regulation. RAPGEF3 plays a role in the GLP1 pathway, which controls insulin secretion in response to blood glucose concentration. Our results highlight the importance of large-scale genomic studies for identifying LFV and RV influencing central fat distribution. Understanding these genetic effects may provide insights into the progression of central adiposity and highlight potential population-specific variants that increase susceptibility.